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Immunotherapy targeting intracellular pathogens

a technology of immunotherapy and intracellular pathogens, applied in the direction of virus peptides, enzymes, biochemistry apparatus and processes, etc., can solve the problems of limited vaccine effectiveness and severe affecting the intracellular survival of bacterial pathogens by tryptophan deprivation

Active Publication Date: 2014-12-25
IMCYSE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to the use of isolated immunogenic peptides for preventing or treating infection with intracellular pathogens. These peptides contain a T-cell epitope derived from the pathogen and a specific motif, which can stimulate non-specific intracellular microbicidal mechanisms in cells infected with the pathogen. The invention covers the use of these peptides for inducing CD4+ regulatory T cells which stimulate non-specific intracellular microbicidal mechanisms. The immunogenic peptides can be used in the manufacture of a medicament for preventing or treating infection with an intracellular pathogen. The invention also includes methods for obtaining a population of intracellular pathogen-associated antigen-specific regulatory T cells with cytotoxic properties.

Problems solved by technology

Hence, vaccine effectiveness remains limited.
Tryptophan deprivation can severely affect the intracellular survival of bacterial pathogens such as Chlamydiae.

Method used

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  • Immunotherapy targeting intracellular pathogens

Examples

Experimental program
Comparison scheme
Effect test

example 1

Cytotoxic Regulatory T Cells to Adenovirus Elicit Increased Generation of Reactive Oxygen Intermediates in Dendritic Cells Presenting the Cognate Peptide

[0104]Adenovirus of serotype 5 (Ad.RR5, E1 / E3-deleted) was used in these experiments. Thus, 5 μL of a solution containing 2×1011 viral particles / ml was administered by the intravenous route to 6 weeks old C57BI / 6 mice. Ten days later, the spleen of such mice was recovered and CD4+ T cells purified by magnetic sorting.

[0105]A T cell epitope was identified within the sequence of the major capsid protein, by a combination of algorithms. A T cell epitope encompassing amino acid residues 912-921 was selected, with sequence: PTLLYVLFEV (SEQ ID NO:1; natural epitope). A synthetic peptide encoding this natural epitope sequence was obtained. A second peptide additionally containing a thioreductase consensus sequence (or redox motif) was synthesised and has the sequence: CHGCPTLLYVLFEV (SEQ ID NO:2; redox motif underlined; modified epitope).

[...

example 2

Mycobacterium tuberculosis

[0109]Mycobacterium tuberculosis is responsible for thousands of deaths every year. The only available vaccination, the Calmette-Guérin mycobacterium bovis-based vaccine (BCG), is not efficient. In addition, several mycobacterium strains show resistance to conventional chemotherapy. Antigen-specific CD4+ cells are known to occur in tuberculosis (Winslow et al. (2003) J. Immunol. 170:2046-2052), which can be protective (Khader et al. (2007) Nature Immunol. 8:369-377).

[0110]The early secretory antigen (ESA) produced by M. tuberculosis is one of the main antigens recognised both by humans and animals such as mice. A dominant T cell epitope, called ESAT-6, corresponding to the amino acid sequence 1-20, has been mapped and shown to be promiscuous, as it activates CD4+ T cells in major mouse strains and in humans. A (natural) T-cell epitope has been identified that contains amino acids 3-17, with sequence: FAGIEAAAS (SEQ ID NO:3). Addition of a consensus sequenc...

example 3

Plasmodium falciparum

[0116]Plasmodium falciparum is a parasite responsible for malaria. The disease develops after mosquito biting. Infected mosquitoes inject sporozoites from Plasmodium into the bloodstream, which are taken by hepatocytes in which they transform into the merozoite form. Upon lysis of hepatocytes merozoites are taken up by erythrocytes, which results in massive hemolysis.

[0117]There is no satisfying vaccine available and malaria is responsible for ±1 million deaths a year, despite the use of chemicals to which the parasite often becomes resistant, such as nivaquine.

[0118]There are two steps at which vaccination could be envisaged (De Groot et al. (1989) J. Immunol. 142, 4000-4005; Reece et al. (2004) Nature Med. 10, 406-410). Prevention could be best obtained if the sporozoite form of the parasite was prevented from invading hepatocytes. Attenuation of ongoing disease could be achieved by targeting the merozoite form to prevent erythrocyte entry. Current efforts in...

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Abstract

The present invention relates to the use of immunogenic peptides comprising a T-cell epitope derived from an intracellular pathogen-associated antigen and a redox motif such as C-(X)2-[CST] or [CST]-(X)2-C in the prevention and / or treatment of infection with an intracellular pathogen and in the manufacture of medicaments therefore.

Description

[0001]This application is a divisional of U.S. application Ser. No. 12 / 735,742 (pending), filed Aug. 13, 2010 (published as US 2012-0009678 A1), which is a U.S. National Phase of International Application No. PCT / EP2009 / 051808, filed Feb. 16, 2009, which claims benefit of U.S. Provisional Application No. 61 / 035,890, filed Mar. 12, 2008 and European Patent Application No. 08447009.5, filed Feb. 14, 2008, the entire contents of each of which is incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention relates to immunogenic peptides and their use in preventing and / or treating infection with intracellular pathogens.BACKGROUND OF THE INVENTION[0003]Numerous infectious diseases are due to microorganisms with an essentially intracellular life cycle. Examples are viral diseases such as influenza, mycobacterium infections such as tuberculosis, bacterial infections such as Mycoplasma and parasitic diseases such as Leishmania and malaria.[0004]Current vaccination proc...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12N9/02C07K14/445A61K39/21C12N7/00A61K39/145C07K14/35C07K14/005
CPCC12N9/0051C07K14/35C07K14/445C07K14/005C12N7/00C12Y108/01009A61K39/21C12N2760/16034C12N2740/16034C07K2319/003A61K39/145A61K39/00A61K39/385A61K2039/57A61K2039/6031A61K2039/64C12N2710/10022C12N2740/16022C12N2760/16022C07K2319/00
Inventor SAINT-REMY, JEAN-MARIE
Owner IMCYSE
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